The central objectives of this research proposal are to characterize and identify the antigen-antibody systems in systemic lupus erythematosus and other autoimmune diseases. Attempts will be made to determine if these antigen-antibody systems are involved in the pathogenesis of tissue injury seen in these diseases. A key approach is the use of human disease sera which spontaneously contain monospecific antinuclear antibodies. These sera will be used as reagents to identify and isolate nuclear macromolecules with antigenic propertes. By immunological techniques, several antigenic nuclear macromolecules have been identified by many investigators and these are DNA, deoxyribonucleoprotein, Sm antigen (alpha nuclear acidic protein devoid of RNA), nuclear ribonucleoprotein and a nucleolar RNA component. Some of these nuclear antigens have been only partially characterized and we anticipate that with the use of spontaneously occurring antibodies in human disease, it would be possible to isolate these antigens in more purified form and characterize them chemically. In looking for pathogenic mechanisms, we propose to use experimental animal models in order to learn more about human disease counterparts.